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Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting

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Science China(Life Sciences) 2022年第2期65卷 328-340页

作者： Bing jiang Xiaohua jia tianjiao ji Meng Zhou jiuyang He Kun Wang jie Tian Xiyun Yan Kelong Fan Nanozyme Medical Center School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Key Laboratory of Molecular Imaging of Chinese Academy of Sciences Institute of AutomationChinese Academy of SciencesBeijing 100190China CAS Key Laboratory for Biomedical Effects of Nanomaterials&Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of MedicineBeihang UniversityBeijing 100191China

Engineered nanocarriers have been widely developed for tumor theranostics.However,the delivery of imaging probes or therapeutic drugs to the tumor pre-formation site for early and accurate detection and therapy remains a major challenge.Here,by using tailor-functionalized human H-ferritin(HFn),we developed a triple-modality nanoprobe IRdye800-M-HFn and achieved the early imaging of tumor cells before the formation of solid tumor tissues.Then,we developed an HFn-doxorubicin(Dox)drug delivery system by loading Dox into the HFn protein cage and achieved early-stage tumor therapy.The intravenous injection of HFn nanoprobes enabled the imaging of tumor cells as early as two days after tumor implantation,and the triple-modality imaging techniques,namely,near-infrared fluorescence molecular imaging(NIR-FMI),magnetic resonance imaging(MRI),and photoacoustic imaging(PAI),ensured the accuracy of detection.Further exploration indicated that HFn could specifically penetrate into pre-solid tumor sites by tumor-associated inflammation-mediated blood vessel leakage,followed by effective accumulation in tumor cells by the specific targeting property of HFn to transferrin receptor 1.Thus,the HFn-Dox drug delivery system delivered Dox into the tumor pre-formation site and effectively killed tumor cells at early stage.IRDye800-M-HFn nanoprobes and HFn-Dox provide promising strategies for early-stage tumor diagnosis and constructive implications for early-stage tumor treatment.

关键词： ferritin nanocage early theranostics tumor-associated inflammation multimodality tumor imaging drug delivery

Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988,1994 and 2007 in Beijing,China

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Virologica Sinica 2022年第2期37卷 168-176页

作者： Junhan Li Fang Huang Yong Zhang tianjiao ji Shuangli Zhu Dongyan Wang Zhenzhi Han jinbo Xiao Fenfen Si Wenbo Xu Dongmei Yan National Polio Laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosecurityNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Nanguan District Center for Disease Control and Prevention Changchun130042China Beijing Center for Disease Control and Prevention Beijing100000China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan430000China

Coxsackievirus A24 variant(CVA24v)is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis(AHC).In China,the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988,followed by another two significant outbreaks respectively in 1994 and 2007,which coincides with the three-stage dynamic distribution of AHC in the world after 1970s.To illustrate the genetic characteristics of CVA24v in different periods,a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed.Compared with the prototype strain,the 23 strains shared four nucleotide deletions in the 5'UTR except the 0744 strain isolated in 2007.And at the 98th site,one nucleotide insertion was found in all the strains collected from 2007.From 1994 to 2007,amino acid polarity in the VP1 region at the 25th and the 32nd site were changed.Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III(GIII),and 2007 strains to Genotype IV(GIV).According to the Bayesian analysis based on complete genome sequence,the most recent common ancestors for the isolates in1988,1994 and 2007 were respectively estimated around October 1987,February 1993 and December 2004.The evolutionary rate of the CVA24v was estimated to be 7.45×10^(-3) substitutions/site/year.Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII.Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak.CVA24v has been evolving constantly with a relatively rapid rate.

关键词： Coxsackievirus A24 variant(CVA24v) Acute hemorrhagic conjunctivitis(AHC) Phylogenetic analysis Complete genome sequence

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai,China,2016–2020

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Virologica Sinica 2022年第2期37卷 177-186页

作者： jiayu Wang jiajing Liu Fanghao Fang jiajin Wu tianjiao ji Yuying Yang Ling Liu Chongshan Li Wanju Zhang Xi Zhang Zheng Teng Microbiology Department Shanghai Municipal Center for Disease Control and PreventionShanghai200336China Microbiology Department Songjiang District Center for Disease Control and PreventionShanghai201620China WHO WPRO Regional Polio Reference Laboratory NHC Key Laboratory for BiosafetyNHC Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China

Coxsackievirus A10(CVA10)is one of the major causative agents of hand,foot and mouth disease(HFMD).To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai,China,we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020.In the past five years,CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%.The annual distribution experienced significant fluctuations over the past five years.In addition to entire VP1 sequencing,complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed.A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis.The CVA10sequences in this study mainly belonged to genogroup C and presented 91%-100%nucleotide identity with other Chinese isolates based on VP1 region.For the first time,our study reported the appearance of CVA10 genogroup D in Chinese mainland,which had led to large-scale outbreaks in Europe previously.The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt,which suggesting intertypic recombination with CVA16 genogroup D.To conclusion,CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020.CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland.Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.

关键词： Coxsackievirus A10(CVA10) Genogroup D Intertypic recombination Hand foot and mouth disease(HFMD)

Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition

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药学学报:英文版 2023年第9期13卷 3849-3861页

作者： Chen Li jiayan Lang Yazhou Wang Zhaoxia Cheng Mali Zu Fenfen Li jingyi Sun Yating Deng tianjiao ji Guangjun Nie Ying Zhao CAS Key Laboratory for Biomedical Effects of Nanomaterials&Nanosafety CAS Center of Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Pancreas Centre the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Green Catalysis Center and College of ChemistryZhengzhou UniversityZhengzhou 450001China School of Basic Medical Sciences Zhengzhou UniversityZhengzhou 450001China

As a representative chemotherapeutic drug,docetaxel(DTX)has been used for breast cancer treatment for decades.However,the poor solubility of DTX limits its efficacy,and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4(CXCR4)expression during the treatment.Herein,we conjugated CXCR4 antagonist peptide(CTCE)with DTX(termed CTCE-DTX)as an anti-metastasis agent to treat breast cancer.CTCE-DTX could selfassemble to nanoparticles,targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy.Thus,the CTCE-DTX NPs achieved promising efficacy on inhibiting both bonespecific metastasis and lung metastasis of triple-negative breast cancer.Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

关键词： Triple-negative breast cancer CXCR4 Docetaxel Drug delivery Peptide-drug conjugates Tumor metastasis Drug formulation

Construction of meloxicam and bupivacaine co-delivery nanosystem based on the pathophysiological environment of surgical injuries for enhanced postoperative analgesia

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Nano Research 2023年第12期16卷 13301-13308页

作者： Mohan Li Yumiao He Zongran Liu Xu Ma Fengrun Sun Lijian Pei Chao Ma Hongju Liu tianjiao ji Yuguang Huang Department of Anesthesiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center of Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Department of Human Anatomy Histology and EmbryologyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China

Besides peripheral nerve injury,the acute inflammation is one of the pathological features of tissues after surgery,which exacerbates the postoperative pain,especially in the first 48 h after the surgery.Multimodal analgesia(MMA),such as the combination of non-steroidal anti-inflammatory drugs(NSAIDs)with local anesthetics,has shown enhanced potency compared with the usage of local anesthetics alone.However,rare formulations can provide long-term analgesia at a single dose.Herein,bupivacaine(BUP,a local anesthetic)loading poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPB)were coated with meloxicam(MLX,an NSAID)loading lipid bilayer(LPM),forming a core–shell nanosystem(NPB@LPM)to provide enhanced and long-term analgesia to treat postoperative pain.MLX was encapsulated in the lipid shell,which enabled high dose MLX to be released in the first 48 h after surgery to reduce the acute inflammation induced pain.BUP was encapsulated in the PLGA core to provide a long-term release for the nerve block.This nanosystem provided a 7-day(whole recovery cycle)effective analgesia in the Brennan’s plantar incision rat model.The tissue reactions of NPB@LPM are benign.This work will provide feasible strategies on designing drug delivery systems for postoperative pain management.

关键词： core–shell nanostructure multimodal analgesia co-delivery system postoperative pain management

Molecular Epidemiology of Echovirus 18 Circulating in China's Mainland from 2015 to 2016

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Virologica Sinica 2019年第1期34卷 50-58页

作者： Xiangpeng Chen tianjiao ji jiayun Guo Wei Wang Wenbo Xu Zhengde Xie Key Laboratory of Major Diseases in Children Ministry of EducationNational Clinical Research Center for Respiratory DiseasesBeijing Key Laboratory of Pediatric Respiratory Infection DiseasesVirology LaboratoryBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health WHO WPRO Regional Polio Reference Laboratory and Key Laboratory of Medical Virology and Viral Diseases National Health and Family Planning Commission of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention

Echovirus 18(E18), a serotype of Enterovirus B(EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in China's Mainland, but became the predominant pathogen associated with viral encephalitis(VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in China's Mainland, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease(HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from China's Mainland after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 50-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiplerecombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.

关键词： Genetic characteristics Echovirus 18 (E18) Genome Enterovirus Recombination

Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

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Science China(Life Sciences) 2022年第12期65卷 2517-2526页

作者： Zhe Chen Linlin Bao Bin Zhu Hua Fu Shuangli Zhu tianjiao ji Ying Xue Chuan Liu Xurong Wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong Liu Qi jin MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China School of Computer Science and Engineering Hunan University of Science and TechnologyXiangtan 411201China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua UniversityBeijing 100084China Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityChangsha 410081China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310058China

Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to death.Currently,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are available.Here,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in cells.The cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of VP1.In a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic treatment.In particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.

关键词： enterovirus A71 antibody mouse models cryo-electron microscopy

基于分层约束强化学习的综合能源多微网系统优化调度

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电工技术学报 2024年第5期39卷 1436-1453页

作者：董雷杨子民乔骥陈盛王新迎蒲天骄华北电力大学电气与电子工程学院北京102206 中国电力科学研究院有限公司北京100192

构建多微网系统是消纳可再生能源、提升电网稳定性的有效方式。通过各微网的协调调度,可有效提升微网的运行效益以及可再生能源的消纳水平。现有多微网优化问题场景多元,变量众多,再加上源荷不确定性及多微网主体的数据隐私保护等问题,... 详细信息

构建多微网系统是消纳可再生能源、提升电网稳定性的有效方式。通过各微网的协调调度,可有效提升微网的运行效益以及可再生能源的消纳水平。现有多微网优化问题场景多元,变量众多,再加上源荷不确定性及多微网主体的数据隐私保护等问题,为模型的高效求解带来了巨大挑战。为此,该文提出了一种分层约束强化学习优化方法。首先,构建了多微网分层强化学习优化框架,上层由智能体给出各微网储能优化策略和微网间功率交互策略;下层各微网以上层策略为约束,基于自身状态信息采用数学规划法对各微网内部的分布式电源出力进行自治优化。通过分层架构,减小通信压力,保护微网内部数据隐私,充分发挥强化学习对源荷不确定性的自适应能力,大幅提升了模型求解速度,并有效兼顾了数学规划法的求解精度。此外,将拉格朗日乘子法与传统强化学习方法相结合,提出一种约束强化学习求解方法,有效地解决了传统强化学习方法难以处理的约束越限问题。最后通过算例验证了该方法的有效性和优势。

关键词：多微网系统分层约束强化学习不确定性数据隐私保护

考虑多重不确定性与电碳耦合交易的多微网合作博弈优化调度

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电工技术学报 2024年第9期39卷 2635-2651页

作者：董雷李扬陈盛乔骥蒲天骄华北电力大学电气与电子工程学院北京102206 中国电力科学研究院有限公司北京100192

双碳背景下,构建低碳运行的能源系统是实现“双碳”目标的重要方向与实施路径。为了促进多微网系统内部能源的本地消纳以及低碳经济运行,该文对不确定性环境下多微网系统的合作运行及电碳耦合交易展开研究。首先,对于每个微网,构建了电... 详细信息

双碳背景下,构建低碳运行的能源系统是实现“双碳”目标的重要方向与实施路径。为了促进多微网系统内部能源的本地消纳以及低碳经济运行,该文对不确定性环境下多微网系统的合作运行及电碳耦合交易展开研究。首先,对于每个微网,构建了电转气碳捕集系统相耦合的热电联产运行模式,基于地方碳交易市场和阶梯碳交易机制,提出了多能源微网的低碳运行模型;其次,考虑到新能源发电和电力市场电价都存在不确定性的实际情况,采用机会约束和鲁棒优化的方法,以降低不确定性影响;再次,基于纳什谈判理论,建立了多个微网电碳耦合的合作博弈模型,各微网主体可同时参与到上级能源市场和地方能源市场中进行电能和碳排放配额的交易;最后,将非凸的合作博弈问题分解为两个线性可求解的子问题,进一步采用交替方向乘子法对问题进行求解。通过算例验证,该文所提方法可以有效提升各微网经济效益并减少碳排放。

关键词：电碳耦合交易纳什谈判合作博弈多微网优化调度